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In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, similar to 50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.

A monochromator integrating-sphere-based spectral comparator facility has been developed to calibrate standard radiation thermometers in terms of the absolute spectral radiance responsivity, traceable to the PTB cryogenic radiometer. The absolute responsivity calibration has been improved using a 75 W xenon lamp with a reflective mirror and imaging optics to a relative standard uncertainty at the peak wavelength of approximately 0.17 % (k = 1). Via a relative measurement of the out-of-band responsivity, the spectral responsivity of radiation thermometers can be fully characterized. To verify the calibration accuracy, the absolutely calibrated radiation thermometer is used to measure Au and Cu freezing-point temperatures and then to compare the obtained results with the values obtained by absolute methods, resulting in T − T90 values of +52 mK and −50 mK for the gold and copper fixed points, respectively.

The primary task of light sources is illumination, i.e., the emission of visible radiation—light. However, depending on the generation principle, besides light, also heat will be dissipated to the surroundings. Traditional thermal light sources generate light by the electrical heating of a tungsten wire to temperatures of about 3000 K. Even at this high temperature, the majority of the emitted thermal radiation is within the long wavelength range of the spectrum, i.e., not in the visible range of the optical spectrum. Generation of light with discharge lamps is completely different and non-thermal; however, even in this case the electrodes are heated to temperatures well above 2000 K. Thus, discharge lamps also suffer from thermal problems. In the case of solid-state light sources, also non-thermal light sources, the driving electrical current causes heating of the device, for which the temperature is, or should usually be, below 420 K for proper operation. Contrary to thermal or discharge light sources, such relatively low temperatures of solid-state light sources prevent efficient cooling by thermal radiation, requiring convective or conductive cooling. However, for all mentioned light sources, the thermal management, i.e., the adjusting and maintaining of an optimum operation temperature are vital for the efficiency and lifetime of the light sources. This paper deals with the methods of generation and measurement of the thermal load in the respective light sources and discusses ways to optimize the efficiency and lifetime of such light sources. Also, some practical examples are given to emphasize the relevance of such thermal management for industry, pointing out the potential for future more energy-efficient light source concepts.

The non-contact measurement of temperature by using the emitted thermal radiation has been an innovative field of measurement science and fundamental physics for more than a hundred years. It saw the first highlight in Gustav Kirchhoff’s principle of a blackbody with ideal emission characteristics and culminated in Max Planck’s formulation of the law of thermal radiation, the so-called Planck’s law, forming the foundation of quantum physics. A boost in accuracy was the development of semiconductor detectors and the cryogenic electrical substitution radiometer in the late 1970s. Semiconductor detectors, namely photodiodes, deliver an electrical current proportional to the absorbed optical radiation. Due to the measurements of thermal radiation over a wide range of temperature and wavelength, thermodynamic temperature measurements with radiometric methods have set benchmarks to all, the electrical, dimensional and optical metrology. The paper describes the measurement of the spectral responsivity of semiconductor detectors traceable to the SI units and their application for thermodynamic temperature measurement by the absolute measurement of thermal radiation using filter radiometers with calibrated spectral irradiance responsivity.

A radiance camera was used to investigate the radiation field emitted by high-temperature blackbodies and fixed-point cavities up to temperatures of 3000 K. In a first step the applicability of the camera to measure the spectral radiance at such high temperatures was investigated. In a second step the radiation characteristics of several sources were studied using the camera system, in particular, large area fixed-point blackbodies of Cu, Pt–C and ZrC–C. Especially for the ZrC–C fixed points the radiation field at the cavity opening was found to be non-uniform. This observation explains systematic differences in the plateau shape of large aperture eutectic fixed-point cells for radiometers with different fields of view. Using the two-dimensional radiance distribution measured with the camera system the deviation of the temperatures measured with interference filter radiometers and radiation thermometers was studied.

The radiometric calibration spectral source (RCSS) is a very low photon flux radiation source based on an integrating sphere, operated under vacuum and cryogenic conditions, for the testing and calibration of the near infrared multiobject dispersive spectrograph (NIRSpec). NIRSpec itself is a part of the scientific instrumentation of the James Webb Space Telescope. For the traceable calibration of the photon flux emitted by the RCSS in the wavelength range from 0.7 µm to 5 µm, dedicated calibration schemes were developed at PTB. To achieve this goal, the Spectral Radiance Comparator Facility and the Reduced Background Calibration Facility of the PTB have been significantly improved with respect to their detector instrumentation.

BACKGROUND: Cytoreductive peritonectomy with hyperthermic intraoperative chemotherapy (HIPEC) is an established therapy for patients with gastrointestinal, gynaecological metastasised peritoneal carcinomatosis as well as primary peritoneal carcinomatous tumours. METHODS: On the basis of a literature review and our personal experience, selection criteria for peritonectomy are discussed. RESULTS: Computed tomography (CT) scans and diagnostic laparoscopy are not sufficient for the diagnosis of peritoneal carcinomatosis. The combination of fluorodeoxyglucose positron emission tomography (FDG-PET) and CT seems to be the most reliable diagnostic imaging method. In our institution, all patients undergo PET / CT prior to peritonectomy. CONCLUSION: The PET / CT scan may play an important role in forecasting the operability of patients with peritoneal carcinomatosis.

The paper describes the new experimental setup assembled at the PTB for the absolute spectral responsivity measurement of radiation thermometers. The concept of this setup is to measure the relative spectral responsivity of the radiation thermometer using the conventional monochromator-based spectral comparator facility also used for the calibration of filter radiometers. The absolute spectral responsivity is subsequently measured at one wavelength, supplied by the radiation of a diode laser, using the new setup. The radiation of the diode laser is guided with an optical fiber into an integrating sphere source that is equipped with an aperture of absolutely known area. The spectral radiance of this integrating sphere source is determined via the spectral irradiance measured by a trap detector with an absolutely calibrated spectral responsivity traceable to the primary detector standard of the PTB, the cryogenic radiometer. First results of the spectral responsivity calibration of the radiation thermometer LP3 are presented, and a provisional uncertainty budget of the absolute spectral responsivity is given.

Der Einsatz der platinbasierten Polychemotherapie lies die Heilungsraten beim Hodentumor dramatisch steigen: Zunachst wurde die Chemotherapie in fortgeschrittenen Stadien eingesetzt. Seit einiger Zeit hat sie ihren Platz auch bei niedrigen Stadien gefunden, wobei hier alternative Behandlungsoptionen zur Verfugung stehen. Risikofaktoren konnen bei der Entscheidungsfindung helfen.

As the biological behaviour of even early stage renal cell cancer (RCC) strongly correlates with tumor size, it has been argued that the inclusion of RCC up to a maximum diameter of 7 cm into a common subgroup classified as T1 according to the 5th edition of the TNM system would not adequately represent the different biological aggressiveness of these malignancies. Taking this into account, the TNM classification, which now categorizes T1 RCC as T1a and T1b according to a cutoff size of 4 cm, was recently modified. However, only a few larger investigations, mainly based on univariate statistical analyses, that support the suitability of this cutoff are at present available from the literature. Therefore, it was the aim of the present investigation to determine the tumor size that best separates patients with low responses from those with high risk for tumor progression by univariate (log rank test) and multivariate (Cox regression model) statistical analyses. Between 1981 and 2000, 652 patients (443 males and 209 females) underwent tumor nephrectomy in our clinic for the diagnosis of RCC. Of these, 243 patients revealed primary tumors with a local growth not extending beyond the renal capsula at the time of surgery. For the different cutoff levels (starting from 2 cm in increments of 1 cm up to 8 cm) that were selected to subdivide the patients into groups according to the maximum tumor diameter, the correlation between tumor size and overall survival was determined by univariate and multivariate statistical analyses. It became evident that although during univariate analysis the prognostic value of a cutoff size of 4 cm was confirmed, multivariate analysis identified the highest relative risk for cause-specific death (2.93) for patients having tumors larger than 5 cm in maximum diameter. Therefore, the 5 cm cutoff seems to best determine the clinical prognosis of patients undergoing tumor nephrectomy for early stage RCC. The present study demonstrates the need for multivariate statistical approaches when the latest modification of the TNM classification system is critically evaluated.

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception

Purpose Long-term survival is rarely achieved in patients with cisplatin-refractory germ cell cancer (GCT). Both single-agent gemcitabine and oxaliplatin have shown activity in patients who experience relapse or are refractory to cisplatin treatment. This study investigates the activity of a gemcitabine plus oxaliplatin regimen in these patients. Patients and Methods Gemcitabine was administered at a dose of 1,000 mg/m2 on days 1 and 8; oxaliplatin was administered at a dose of 130 mg/m2 on day 1. Response was evaluated every 4 weeks. Results Thirty-five patients with a median age of 37 years (range, 21 to 54 years) were enrolled onto the study. Primary tumor localization was gonadal, retroperitoneal, or mediastinal in 30, one, and four patients, respectively. Patients had been pretreated with a median of six platinum-containing cycles (range, four to 13 cycles) and 89% of patients previously had experienced treatment failure after high-dose chemotherapy with peripheral-blood stem-cell transplantation. Sixty-three percent of patients were considered absolutely cisplatin-refractory or cisplatin-refractory. A median of two cycles (range, 1 to 6 cycles) per patient were applied. Toxicity consisted mainly of myelosuppression, with Common Toxicity Criteria grade 3 occurring in 54% of patients. Only 9% of patients developed neutropenic fever. Three patients attained a complete remission (CR), two patients attained a marker-negative partial remission, and 11 patients attained a marker-positive partial remission, resulting in an overall response rate of 46% (95% CI, 30% to 64%). All three patients with CR and one patient with a marker-negative partial remission remained disease free at 16+, 12+, 4+, and 2+ months of follow-up. Seven (44%) of these 16 responses, including one CR, occurred in cisplatin-refractory patients. Conclusion Gemcitabine plus oxaliplatin demonstrates antitumor activity with acceptable toxicity in heavily pretreated patients with relapsed or cisplatin-refractory GCT, and may offer a chance of long-term survival for selected patients.

Single modality bladder-sparing therapy for muscle-invasive bladder cancer, including transurethral resection (TUR), partial cystectomy, systemic chemotherapy or radiotherapy, have been demonstrated to result in insufficient local control of the primary tumour, as well as decreased long-term survival in the patients when compared to radical cystectomy. Therefore, multimodality treatment protocols that aim at bladder preservation and involve all of the aforementioned approaches have been established. Arguments for combining systemic chemotherapy with radiation are to sensitise tumour tissue to radiotherapy and to eradicate occult metastases that have already developed in as many as 50% of patients at the time of first diagnosis. It has been shown that the clinical outcome observed with this approach approximates that after radical cystectomy. Additionally, a substantial number of patients survive with an intact bladder. However, bladder-sparing approaches are costly, and require close co-operation between different clinical specialists as well as careful follow-up. The good long-term results that are observed after cystectomy and the creation of an orthotopic neobladder make the substantial advantage of a bladder preservation strategy questionable when the patient's quality of life is addressed. Additionally, bladder-sparing therapy-related side effects might result in an increased morbidity and mortality in those patients who need to undergo surgery due to recurrent or progressive disease. Multimodality bladder-sparing treatment is a therapeutic option that can be offered to the patient at centres that have a dedicated multidisciplinary team at their disposal. However, radical cystectomy remains the standard of care for muscle-invasive bladder cancer.

This study compares tumour response assessment by automated CT volumetry and standard manual measurements regarding the impact on treatment decisions and patient outcome.58 consecutive patients with 203 pulmonary metastases undergoing baseline and follow-up multirow detector CT (MDCT) under chemotherapy were assessed for response to chemotherapy. Tumour burden of pulmonary target lesions was quantified in three ways: (1) following response evaluation criteria in solid tumours (RECIST); (2) following the volume equivalents of RECIST (i.e. with a threshold of -65/+73%); and (3) using calculated limits for stable disease (SD). For volumetry, calculated limits had been set at ±38% prior to the study by repeated quantification of nodules scanned twice. Results were compared using non-weighted κ-values and were evaluated for their impact on treatment decisions and patient outcome.In 15 (17%) of the 58 patients, the results of response assessment were inconsistent with 1 of the 3 methods, which would have had an impact on treatment decisions in 8 (13%). Patient outcome regarding therapy response could be verified in 5 (33%) of the 15 patients with inconsistent measurement results and was consistent with both RECIST and volumetry in 1, with calculated limits in 3 and with none in 1. Diagnosis as to the overall response was consistent with RECIST in six patients, with volumetry in six and with calculated limits in eight cases. There is an impact of different methods for therapy response assessment on treatment decisions.A reduction of threshold for SD to ±30-40% of volume change seems reasonable when using volumetry.

To establish precise diagnostic algorithms and standardised treatment of sarcomas in specialized centers, the interdisciplinary research group KoSar (sarcoma competence network) has been funded by German Cancer Aid. A sarcoma tissue repository and a diagnostic reference center have been set up, presently containing about 1000 accurately diagnosed sarcomas of different entities. Significant gene expression profiles for synovial sarcomas, leiomyosarcomas, myxoid liposarcomas and a small profile for myxofibrosarcomas as well as a new classification of angiosarcomas were defined. We systematically searched for activated signal transduction pathways in sarcoma cell lines and xenograft transplant models and candidate targets for molecular therapies were identified. Based on these results first clinical studies have been initiated by the German Interdisciplinary Sarcoma Study Group (GISG).

Background Survival after high-dose chemotherapy (HDCT) as second-salvage treatment (SST) in multiple relapsed germ-cell tumors (GCTs). Patients and methods Existing databases in Berlin and Marburg of HDCT trials from 1989 to 2008 were retrospectively screened. Among 534 patients, 71 of 534 (13%) patients were scheduled for HDCT having failed previous conventional-dose first-line and first-salvage chemotherapy regimens; those 49 patients who had received at least cisplatin plus etoposide first-line as well as conventional-dose cisplatin-based first-salvage regimens and were diagnosed after 1 January 1990 were further analyzed. Results Median age at SST was 32 years (range 19–52 years). Median follow-up for surviving patients was 4 years (range 1.7–8.5 years). Three of 49 (6%) patients either progressed or died before scheduled HDCT; the remaining 46 of 49 (94%) received either single or sequential HDCT. The rate of favorable responses to HDCT was 27 of 49 (55%). Nine patients remain alive and free of progression. One additional patient was lost to follow without progression at 4 years. The projected overall survival rate at 5 years was 17% (95% confidence intervals 7% to 30%). Conclusion HDCT can induce remissions in patients with multiple relapsed GCTs with a long-term survival rate of ∼17%.

The Physikalisch-Technische Bundesanstalt (PTB) has developed dedicated instrumentations and methods for the traceable calibration of space borne instruments in terms of the three fundamental radiometric units, i.e. spectral radiance (radiation temperature), spectral radiant intensity and spectral photon flux. The traceable calibration under conditions similar to the space environment is achieved by use of two major radiometric calibration facilities of PTB, the Spectral Radiance Comparator Facility (SRCF) and the Reduced Background Calibration Facility (RBCF) which are part of the Primary Temperature Radiator Facility of PTB and cover the wavelength range from the UV to the FIR (THz range). The improved detector instrumentations of the SRCF and RBCF, detailed calibration schemes and results of calibrations for space missions are presented.

In 1997, the Consultative Committee for Photometry and Radiometry (CCPR) initiated a supplementary comparison of spectral radiance in the wavelength range from 220 nm to 2500 nm (CCPR-S1) using tungsten strip-filament lamps as transfer standards. Five national metrology institutes (NMIs) took part in the comparison: BNM/INM (France), NIST (USA), NRC (Canada), PTB (Germany) and VNIIOFI (Russia), with VNIIOFI as the pilot laboratory. Each NMI provided the transfer lamps that were used to transfer their measurements to the pilot laboratory. The intercomparison sequence began with the participant measurements, then the pilot measurements, followed by a second set of measurements by the participant laboratory. The measurements were carried out from 1998 to 2002, with the final report completed in 2008. This paper presents the descriptions of measurement facilities and uncertainties of the participants, as well as the comparison results that were analysed in accordance with the Guidelines for CCPR Comparisons Report Preparation, and a re-evaluation of the results taking into account the instability of some of the transfer lamps. Excluding a few wavelengths, all participants agree with each other within ±1.5%. The disagreement decreases to approximately ±1.0% when the anomalous data are excluded from the analysis.

Cytoreductive peritonectomy with hyperthermic intraoperative chemotherapy (HIPEC) is an established therapy for patients with gastrointestinal, gynaecological metastasised peritoneal carcinomatosis as well as primary peritoneal carcinomatous tumours.On the basis of a literature review and our personal experience, selection criteria for peritonectomy are discussed.Computed tomography (CT) scans and diagnostic laparoscopy are not sufficient for the diagnosis of peritoneal carcinomatosis. The combination of fluorodeoxyglucose positron emission tomography (FDG-PET) and CT seems to be the most reliable diagnostic imaging method. In our institution, all patients undergo PET / CT prior to peritonectomy.The PET / CT scan may play an important role in forecasting the operability of patients with peritoneal carcinomatosis.

Low grade endometrial stromal sarcoma (LGESS) is a rare disease. LGESS usually expresses steroidal receptors and is regarded to be hormone-sensitive. Due to the rarity of the tumor, only few case series have been published so far. Here, we report the case of a 36-year-old woman who underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy and adjuvant radiotherapy for a G1 LGESS in 1991. Twelve years later she presented to us with pelvic and peritoneal masses. The patient was treated with letrozole achieving a partial response which is lasting 39 months. Treatment is ongoing. Aromatase inhibitors represent an interesting treatment option for LGESS.

Platinum-based polychemotherapy has increased the cure rate in testicular cancer dramatically: at first, chemotherapy was mainly used in advanced disease. Recently it has also become common in low-stage disease, though other therapeutic options are equivalent. Risk factors might help to find the right decision. The success of treatment in patients with metastatic disease results from the combination of chemotherapy and secondary surgery. High-dose chemotherapy for patients with poor prognosis or recurrent disease is being evaluated in clinical trials. Concerning the success in these stages prognostic factors are of special importance. Patients with advanced-stage nonseminoma need residual tumor resection after chemotherapy if no complete remission could be achieved. The therapist should be aware of the indication for and schedule of chemotherapy, its side effects, and supportive care.

Zu den gutartigen (fakultativ bosartigen) Tumoren der Niere gehoren Nierenadenome und Nierenonkozytome, beide epithelialen Ursprungs, sowie Angiomyolipome oder Mark-Kegel-Fibrome mesenchymalen Ursprungs. Die bosartigen Neoplasien umfassen das Nephroblastom, das uberwiegend im Kindesalter auftritt, sowie das Nierenzellkarzinom. Letzterer ist der haufigste epitheliale maligne Nierentumor des Erwachsenen und macht ca. 2% aller malignen Neubildungen des Erwachsenen aus. Differenzialdiagnostisch kommen noch Sarkome, Lymphome und Metastasen anderer Malignome in Betracht. Durch den zunehmenden Einsatz von bildgebenden Verfahren, v. a. der Sonographie, wird das Nierenzellkarzinom haufig inzidentell beim asymptomatischen Patienten diagnostiziert. Die operative Therapie hat daher in zunehmendem Mase organerhaltende Verfahren entwickelt, die als minimalinvasive, laparoskopische Resektion durchgefuhrt werden. Dies geht mit einer Minderung der Belastung der Patienten durch die Operation einher. Die therapeutischen Fortschritte der Disziplinen Strahlen-, Chemo-, Hormon- oder Immuntherapie sind gering. Die Prognose der Erkrankung hangt von der Tumorausdehnung ab. Die einzig kurative Behandlung stellt die operative Entfernung dar. Die Behandlungsergebnisse beim metastasierten Nierenzellkarzinom sind nach wie vor schlecht. Der Tumor ist weitgehend chemotherapieresistent, und auch mit hormoneller Therapie nicht beeinflussbar. Die Immuntherapie mit Interferon und Interleukin bzw. deren Kombination zeigen eine gewisse Wirksamkeit, ohne bisher eine unumstrittene klinische Wertigkeit erlangt zu haben. Es existiert kein zuverlassiger Tumormarker zur Diagnose oder zum Verlauf des Nierenzellkarzinoms.

Colorectal carcinoma is the second common cause of death from cancer. For a long period patients with metastatic disease were considered incurable except for a small subgroup with isolated surgically complete removable lesions in the lungs and the liver. Chemotherapy was a treatment of unproven value, beneficial in very few patients. However, in the last two decades it has become a well-documented survival prolonging treatment, postponing tumor symptoms in the majority of patients, and potentially curing some patients if combined with aggressive surgery.

Background: The current two studies evaluate the feasibility, toxicity and efficacy of an adjuvant combined modality treatment strategy containing a three to four-drug chemotherapy regimen plus 5-fluorouracil (FU)-based radiochemotherapy. Patients and methods: Between December 2000 and October 2003, a total of 86 patients were included in both studies. Patients with completely resected gastric adenocarcinoma including a D1 or D2 lymph node dissection (LND) were eligible. Treatment consisted of two cycles of folinic acid 500 mg/m2, 5-FU 2000 mg/m2 continuous infusion over 24 h once weekly for 6 consecutive weeks, paclitaxel 175 mg/m2 in weeks 1 and 4 and cisplatin 50 mg/m2 in weeks 2 and 5 (FLPP; n=41) or two cycles of the same 5-FU/folinic acid schedule but with cisplatin 50 mg/m2 only in weeks 1, 3 and 5 (FLP; n=45). Radiation with 45 Gy plus concomitantly applied 5-FU 225 mg/m2/24 h was scheduled in between the two cycles. Results: Patients characteristics were: D1/D2 LND FLP group 53%/42%; FLPP group 27%/68%; stage distribution: UICC stages III/IV(M0) FLP group 63% and FLPP group 66%. Median follow-up was 10 months (3–25) for FLP and 18 months (2–51) for FLPP patients. CTC grade 3/4 toxicities during the first cycle/chemoradiation/second cycle of FLP: granulocytopenia 3%/0/27%, anorexia 6%/10%/8%; diarrhea 8%/0/4%, nausea 3%/0/4%; FLPP: granulocytopenia 0/0/37%, anorexia 5%/11%/6%; diarrhea 5%/0/3, nausea 3%/8%/0%; early death in one patient due to Pneumocystis carinii pneumonia. Projected 2-year progression-free survival was 64% (95% CI 56% to 68%) for the FLP and 61% (95% CI 42% to 78%) for the FLPP group. Conclusions: Both chemoradiation regimens appear feasible with an acceptable toxicity profile indicating that cisplatin can be added to 5-FU/FA and that even a four-drug regimen can be investigated further in prospective clinical trials in completely resected gastric cancer patients. Treatment should be given in experienced centres in order to avoid unnecessary toxicity.

The neuro-endocrine tumors of the gastrointestinal tract comprise a heterogeneous group of slow-growing malignancies with great differences regarding their localization, tissue of origin and their entopic and ectopic production of hormones. They can be subdivided in carcinoid tumors and endocrine tumors of the pancreas. According to their secreted products they manifest as endocrinological syndromes or as local space-occupying tumors. This review focuses, besides summarizing the available epidemiological data and describing tumor localization and classification, on the differing symptom complexes and the prognosis of the various tumor entities. Furthermore, the value of available diagnostic techniques and the role of different therapeutic modalities like surgery, radiation, biotherapy and cytostatic chemotherapy are discussed.

Although the leading platinum compounds, cisplatin, carboplatin, and oxaliplatin, share some structural similarities, there are marked differences between them in therapeutic uses, pharmacokinetics, and adverse effects profiles. Compared with cisplatin, carboplatin has inferior efficacy in germ-cell tumors, head and neck cancers, and bladder and esophageal carcinomas, whereas the two drugs appear to have comparable efficacy in ovarian cancer, extensive small-cell lung cancers (SCLC), and advanced non-small-cell lung cancers (NSCLC). Oxaliplatin belongs to the group of diaminocyclohexane (DACH) platinum compounds. It is the first platinum-based drug that has marked efficacy in colorectal cancer when given in combination with 5-fluorouracil and folinic acid. Nedaplatin has been registered in Japan, whereas other derivatives, like JM216 (which is the only orally available platinum derivative), ZD0473, BBR3464, and SPI-77 (a liposomal formulation of cisplatin), are still under investigation. The adverse effects of platinum compounds are reviewed together with possible prevention strategies.

Purpose To assess the role of residual tumor resection performed after high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ cell tumors (GCT). Patients and Methods Between July 1987 and October 1999, postchemotherapy resections of residual tumors were performed in 57 patients who had been treated with HDCT for relapsed or refractory GCT and who had achieved a partial remission to this treatment. Results Complete resections of residual masses were achieved in 52 (91%) of 57 patients who were rendered disease free; in five (9%) of 57 patients, the resections were incomplete. Resection of a single site was performed in 39 (68%) of 57 patients, and the remaining 18 (32%) of 57 patients required interventions at two or more residual tumor sites. Necrosis was found in 22 (38%) of 57 patients, mature teratoma with or without necrosis was found in nine (16%) of 57 patients, and viable cancer with or without additional necrosis or mature teratoma was found in 26 (46%) of 57 patients. Viable cancer consisted either of residual germ cell or undifferentiated cancer in 22 (85%) of 26 patients, with additional non-GCT histologies in the remaining four patients. Patients with viable cancer had a significantly inferior outcome after surgery compared with patients with necrosis and/or mature teratoma even if all cancer was completely resected. Pulmonary lesions with a diameter of more than 2 cm were the only predictive variable for viable cancer in univariate analysis. Conclusion Resections of all residual tumors should be attempted in patients with relapsed or refractory GCT and partial remissions after HDCT.

The introduction of cisplatin-based systemic chemotherapy into the clinical routine has resulted in a substantial improvement of the recurrence-free and long-term survival of patients with metastatic testicular germ cell tumors. Late relapses after the completion of first-line therapy, comprising systemic chemotherapeutic treatment in combination with a complete resection of residual tumor masses visible in about 25-50% of patients, have been reported to occur in 1-5% of patients later than 2 years following the initial treatment. It has been reported that the risk for the development of late recurrence is correlated to the tumor burden at first diagnosis and/or the presence of teratomatous components within the primary testicular cancer. Second-line chemotherapy in combination with surgery, although not very well standardized, has been recommended as the most effective therapeutic regimen during the treatment of patients suffering from late recurrent germ cell tumors. Herein, we report our single-center experience with 14 patients in different clinical stages who developed late relapse after successful first-line therapy. In the present series, the risk for late relapse was not correlated to the clinical stage at first diagnosis or the presence of teratomatous elements within the primary tumor. It became evident that in selected cases chemotherapy alone can be considered a curative treatment option.

Overall, patients with relapsed or progressive germ cell tumors after cisplatin-based chemotherapy have a low chance of cure. Using conventional-dose chemotherapy (CDCT) as salvage treatment, only 15-30% of the patients will become long-term survivors. It is well known that the majority of these patients will ultimately die of their disease. Therefore, improvement of the standard treatment is clearly desirable. In the last years, high-dose chemotherapy (HDCT) has been established as an effective salvage modality. A matched-pair analysis showed an advantage for HDCT compared with CDCT with an improvement in event-free and overall survival. Furthermore, due to increasing clinical experience in the management of side-effects, the use of peripheral blood progenitor cells and the availability of hematopoietic growth factors, HDCT has become relatively safe. Therefore, HDCT should be administered in patients with first relapse and unfavorable prognostic factors, and as second or subsequent salvage treatment followed by complete resections of tumor residuals. Patients with relapse or progressive disease after HDCT who do not qualify for desperation surgery could be salvaged with palliative chemotherapy combinations using gemcitabine, oxaliplatin and paclitaxel. This report reviews the current treatment strategies and recent developments with respect to HDCT given as salvage treatment and discusses the role of prognostic factors in the management of such situations.

Purpose: Patients with disseminated germ cell cancer and poor prognosis (International Germ Cell Cancer Collaborative Group [IGCCCG] classification) achieve only a 45% to 50% long-term survival by standard chemotherapy. First-line high-dose chemotherapy might be able to improve the result. This analysis reports toxicity and long-term results of a large phase I/II study of sequential high-dose etoposide, ifosfamide, and cisplatin (VIP) in patients with advanced germ cell tumors. Patients and Methods: Between July 1993 and November 1999, 221 patients with either Indiana “advanced disease” (n = 39) or IGCCCG “poor prognosis” criteria (n = 182) received one cycle of VIP followed by three to four sequential cycles of high-dose VIP chemotherapy plus stem cell support, every 3 weeks, at six consecutive dose levels. Results: Dose limiting toxicity occurred at level 8 (100 mg/m2 cisplatinum, 1750 mg/m2 etoposide, 12 g/m2 ifosfamide) with grade 4 mucositis (three of eight patients), grade 3 CNS toxicity (one of eight patients), grade 4 renal toxicity (one of eight patients), and prolonged granulocytopenia (one of eight patients). After 4-year median follow-up, progression-free survival and disease-specific survival rates in the poor prognosis subgroup were 69% and 79% at 2 years and 68% and 73% at 5 years, with 76% for gonadal/retroperitoneal versus 67% for mediastinal primaries. Severe toxicity included treatment related death (4%), treatment-related acute myeloid leukemia (1%), long-term impared renal function (3%), chronic renal failure (1%), and persistant grade 2–3 neuropathy (5%). Conclusion: Repetitive cycles of high-dose VIP with peripheral stem cell support can be successfully applied in a multicenter setting. Dose level 6 with cisplatin 100 mg/m2, etoposide 1500 mg/m2, and ifosfamide 10 g/m2 is recommended for further investigation in randomized trials. An ongoing randomized trial within the European Organization for Research and Treatment of Cancer evaluates this protocol against four cycles of standard cisplatin, etoposide, and bleomycin.

The number of cytostatic agents effective in patients with advanced soft tissue sarcoma is limited. Trofosfamide, an alkylating agent, has been shown to be effective in several solid and haematological tumors.Eighteen patients with a median age of 57 years (range, 27-78) were treated with oral trofosfamide 300 mg/d for 1 week followed by 150 mg/d given continuously to analyze the efficacy and toxicity of continuous low-dose oral trofosfamide. All had received at least one anthracycline-based chemotherapeutic regimen prior to trofosfamide.Nine patients (50%) achieved stable disease lasting for a median of 5.5+ months (range, 1-9+). The median time to progression was 10+ weeks (range, 4-37+) and the median survival 7+ months (range, 2-13+). Toxicity was mild, grade III degree toxicity was seen in 5 patients (28%): 3/2 patients with anemia/neutropenia and 2 patients with fatigue syndrome.No objective remission was observed with oral low-dose trofosfamide in heavily pretreated soft tissue sarcoma patients, but almost half of the patients achieved disease stabilisation for half a year. The moderate toxicity profile observed in this study allows the consideration of trofosfamide as a reasonable palliative treatment option for patients with soft tissue sarcoma.

The nephrotoxic effects of different platinum compounds based combination chemotherapies were compared. Chemotherapy consisted of either cisplatin fractionated over 5 days (5 x 20 mg/m2) or given as a single-day infusion (1 x 50 mg/m2) plus ifosfamide (4 g/m2) or high-dose chemotherapy was applied including carboplatin (3 x 500 mg/m2) and ifosfamide (3 x 4 g/m2) fractionated over three consecutive days. Conventional parameters such as serum creatinine and glomerular filtration rate (GFR), as well as urinary protein excretion of N-acetyl-beta-D-glucosaminidase (NAG)) and alpha 1-micro-globulin were assessed in 52 patients. Fractionation over 5 days without adding other nephrotoxic agents, i.e. ifosfamide, prevented decreases in GFR following cisplatin, whereas the combination of conventional dose cisplatin and ifosfamide, given as a single-day infusion, and high-dose carboplatin/ifosfamide yielded a pronounced fall of GFR. All groups showed increases in the urinary excretion levels of serum derived proteins and NAG, but with significant differences; about 2 to 3-fold for 5-days cisplatin, 3 to 5-fold for single-day cisplatin/ifosfamide, and 20 to 35-fold for high-dose chemotherapy. Thus, conventional approaches can reduce but not prevent the nephrotoxicity of cisplatin-based chemotherapy. In particular, high-dose chemotherapy regimens including carboplatin and ifosfamide are associated with comparable or even higher nephrotoxicity to single-day cisplatin/ifosfamide. In the light of the long-term consequences of persistent renal damage prevention of nephrotoxicity should be further improved.

An experimental facility is presented, which allows calibration and detailed investigation of infrared camera systems. Various blackbodies operating in the temperature range from -60 degree(s)C up to 3000 degree(s)C serve as standard radiation sources, enabling calibration of camera systems in a wide temperature and spectral range with highest accuracy. Quantitative results and precise long-term investigations, especially in detecting climatic trends, require accurate traceability to the International Temperature Scale of 1990 (ITS-90). For the used blackbodies the traceability to ITS- 90 is either realized by standard platinum resistance thermometers (in the temperature range below 962 degree(s)C) or by absolute and relative radiometry (in the temperature range above 962 degree(s)C). This traceability is fundamental for implementation of quality assurance systems and realization of different standardizations, for example according ISO 9000. For investigation of the angular and the temperature resolution our set-up enables minimum resolvable (MRTD) and minimum detectable temperature difference (MDTD) measurements in the various temperature ranges. A collimator system may be used to image the MRTD and MDTD targets to infinity. As internal calibration of infrared camera systems critically depends on the temperature of the surrounding, the calibration and investigation of the cameras is performed in a climate box, which allows a detailed controlling of the environmental parameters like humidity and temperature. Experimental results obtained for different camera systems are presented and discussed.

The palliation of symptoms and improvement of quality of life are important aspects of therapy in patients with incurable metastatic cancer. This article describes the preliminary results of a phase I study of uracil and tegafur, an orally available fluorouracil (5-FU) derivative combined with oral leucovorin plus weekly intravenous paclitaxel. While the daily oral dose of UFT is fixed at 300 mg/m2 plus 90 mg leucovorin on days 1 to 28, paclitaxel is escalated in 10 mg/m2 steps starting with 50 mg/m2 weekly as a 1-hour infusion. To date, 26 patients with a median age of 57 years have been entered into the protocol and have received a median 2.2 cycles of therapy. Dose level 4 (paclitaxel 80 mg/m2) has been recently completed. Major dose-limiting toxicities were fatigue syndrome (two patients) and diarrhea (five patients). Preliminary responses have been observed in three of 14 currently evaluable patients. This protocol is taking the development of protracted 5-FU administration--given orally as UFT--in combination with paclitaxel one step further, using paclitaxel in a dose-dense, weekly schedule. It is hoped that an active regimen for the outpatient treatment of solid tumors will be developed.

Given the young age at which testicular cancer is treated and the excellent prognosis for patients suffering from this disease, therapy-related malignancies represent a significant problem. Therapy-related solid tumors are associated mainly with the use of radiation therapy. The risk for developing a therapy-related solid tumor is approximately 2- to 3-fold increased compared with the general population. Therapy-related leukemias are associated predominantly with chemotherapy, particularly with the use of topoisomerase-II inhibitors and alkylating agents. In general, the cumulative incidence of therapy-related leukemia is low. It is approximately 0.5% and 2% at 5 years of median follow-up for patients receiving etoposide at cumulative dosesor = 2 g/m2 and2 g/m2, respectively. High cumulative doses of etoposide given over a short period of time appear to be less leukemogenic than a similar dose of etoposide given over a longer period of time. There might, additionally, be a synergistic effect of cisplatin and etoposide on the induction of therapy-related leukemia. For patients who receive high-dose chemotherapy with autologous stem-cell support, the risk of therapy-related myelodysplastic syndrome and leukemia appears to be substantially lower compared with that reported in non-Hodgkin's lymphoma patients undergoing high-dose chemotherapy. The transplantation procedure itself does not appear to add to the therapy-related leukemia risk. The risk-benefit analysis in patients with testicular cancer clearly favors the use of current treatment regimens including high-dose chemotherapy. However, even the acceptably low number of therapy-related leukemias should encourage the search for equally effective but less toxic therapies.